Maternal serum is screened during the second trimester for elevations in alpha-fetoprotein, which may indicate that the fetus has an open neural tube defect. alpha-Fetoprotein is a glycoprotein synthesized in the fetus, and it appears in the amniotic fluid and maternal serum. With an open neural tube defect involving the fetus, AFP can show increased leakage into the amniotic fluid and maternal serum. If an elevated maternal AFP relative to the gestational age is detected, more definitive tests are performed in order to find the cause for the elevation.


Since maternal serum AFP levels increase during pregnancy after 12-13 weeks of gestation, the gestational timing of the pregnancy is important. Because of variability in testing between laboratories, each laboratory much determine the median value for the normal reference interval for each gestational date. Often a sample is tested twice, and the average of the two determinations is used as the test result.


Specimen: maternal serum, usually during weeks 16-to-18 week of gestation, although testing may be done from 15-to-20 weeks.


multiple of the mean = MoM =

= (average of maternal serum AFP determinations) / (median of the normal reference interval at the testing laboratory for stated gestational age in weeks)


Correction for maternal weight:

(1) since the maternal plasma volume changes with body size, a given amount of AFP produced by the fetus will vary proportionate to body weight.

(2) correction factor = 10 ^ (0.2658 - (0.00188 * (maternal weight in pounds)))

(3) this is divided into the uncorrected MoM

(4) in women with high body weights, the adjustments may be too high resulting in false positive findings. The cut-off for making the adjustment varies, with 200, 250 or 280 pounds used as the upper limit for adjustments (250 pounds is used in the spreadsheet).

(5) in women with low body weights, the lowest weight used for the equation is 90 pounds


Correction for Black race:

(1) Black women tend to have higher maternal serum AFP levels than White women. This varies from 10-15% higher.

(2) correction factor = 1.1

(3) the correction factor is divided with the uncorrected MoM

(4) a variation is to multiply the MoM by 0.9 (= 1/1.1)


Correction for insulin dependent diabetes:

(1) in mothers with insulin-dependent diabetes preceding pregnancy, maternal serum AFP levels are 20-40% lower than for normoglycemic mothers

(2) correction factor = 0.7 or 0.8

(3) the correction factor is divided into the uncorrected MoM.


Correction for multiple gestations:

(1) in twin gestations, divide 2.13 into the uncorrected MoM

(2) in triplet gestations, divided 2.9 into the uncorrected MoM



• The upper limit of normal varies with the institution, but typically is 2.5 MoM.

• The lower limit of normal varies with the institution, but typically is 0.4 MoM.


Causes of elevated maternal serum AFP included (partial listing given):

(1) open neural tube defects

(2) fetal blood contamination

(3) multiple gestations (twins, triplets. etc.)

(4) incorrect gestational age

(5) congenital nephropathies

(6) duodenal or esophageal atresia

(7) hydrops fetalis

(8) threatened abortion

(9) body wall defects (omphalocele, etc.)

(10) fetal death

(11) Turner's Syndrome

(12) congenital tumors

(13) maternal liver disease

(14) maternal AFP-producing neoplasms

(15) maternal ataxia-telangiectasia


Causes of a low maternal serum AFP:

(1) Down Syndrome or other trisomy


Causes for a falsely lower maternal serum AFP:

(1) maternal insulin-dependent diabetes (unless corrected as above)

(2) maternal obesity (unless corrected as above)



• The gestational age information must be accurate for correct interpretations.

• Variation exists between laboratories.


Followup testing:

(1) verification of gestational age for pregnancy

(2) repeat maternal serum AFP level determination, 1 week after the initial test.

(3) ultrasound for neural tube defect

(4) amniotic fluid sampling for AFP, acetylcholinesterase and karyotyping.


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